The report from the COVID Moonshot Consortium highlights the discovery of novel inhibitors against the major proteases of SARS-CoV-2. This global collaboration has resulted in a promising lead compound and thousands of compound designs have been publicly shared, marking significant progress in coronavirus drug development. COVID Moonshot's breakthrough research introduces new non-peptide inhibitors for SARS-CoV-2, demonstrating the role of global collaboration and open science in advancing the coronavirus**.
Although the work of the research group has been available free of charge since its inception in March 2020, the Covid Moonshot Coalition has finally officially reported its results. This is an open-science, crowdsourced, and patent-free drug discovery campaign targeting the SARS-CoV-2 virus, and it has already gained a wealth of data on the virus's major proteases, including insights that could pave the way for the development of better new**.
Brian Shoichet and Charles Craik wrote in a related Perspectives article:"Given the timelines and challenges of drug approval, the lead** described by [these researchers] may not be able to impact the current pandemic in a timely manner. "Still, these compounds and the technology used to identify them are likely to affect human health in the future"。
This novel collaboration includes more than 200 volunteer scientists from 47 academic and industrial organizations in 25 countries. Melissa and colleagues wrote:"COVID Moonshot has advanced infectious disease drug discovery by providing an example of open science drug discovery – an area of research of great public significance, but chronically underfunded by the private sector. "
Due to the important role of SARS-CoVb-2 major protease (mPRO) in viral replication, it is an attractive target for antiviral development. Current SARS-CoV-2 mpro inhibitor drugs, such as those extracted from existing antiviral product lines such as Paxlovid and Xocova, have been clinically successful. However, the use of these compounds is still relatively limited, and their peptidomimetic and covalent scaffolds pose problems for synthesis and administration.
In this paper, Boby et al. describe the discovery of a novel, non-covalent, non-peptide inhibitor scaffold that is chemically distinct from current mPRO inhibitors. Drawing on a crowdsourced approach and the expertise of hundreds of people around the world, Boby et al. described their open-science drug discovery campaign, which included machine Xi, molecular simulation, high-throughput structural biology, and chemistry to map the structure of the major SARS-CoV-2 proteases and their biochemical activities.
Among the more than 18,000 compounds designed by the Covid Moonshot Consortium, the authors identified several non-covalent, non-peptidomimetic inhibitors, including a lead compound with good bioavailability, safety, and antiviral activity.
All compound designs for the project have been publicly shared, creating a rich, open, and IP-free knowledge base for future anti-coronavirus drug discovery.
Related Literature: doi: 101126/science.abo7201
Compilation**: scitechdaily